Gain-of-function analogues of the pore-forming peptide melittin selected by orthogonal high-throughput screening.

ABSTRACT: We recently developed an orthogonal, high-throughput assay to identify peptides that self-assemble into potent, equilibrium pores in synthetic lipid bilayers. Here, we use this assay as a high-throughput screen to select highly potent pore-forming peptides from a 7776-member rational combinatorial peptide library based on the sequence of the natural pore-forming peptide toxin melittin. In the library we varied ten critical residues in the melittin sequence, chosen to test specific structural hypotheses about the mechanism of pore formation. Using the new high-throughput assay, we screened the library for gain-of-function sequences at a peptide to lipid ratio of 1:1000 where native melittin is not active. More than 99% of the library sequences were also inactive under these conditions. A sm

SUBMITTER: Krauson AJ 

PROVIDER: S-EPMC3443472 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature